Use of Computational Biochemistry for Elucidating Molecular Mechanisms of Nitric Oxide Synthase
Nitric oxide (NO) is an essential signaling molecule in the regulation of multiple cellular processes. It is endogenously synthesized by NO synthase (NOS) as the product of L-arginine oxidation to L-citrulline, requiring NADPH, molecular oxygen, and a pterin cofactor. Two NOS isoforms are constituti...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-01-01
|
| Series: | Computational and Structural Biotechnology Journal |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2001037018303465 |
| _version_ | 1818481382707429376 |
|---|---|
| author | Emmanuelle Bignon Salvatore Rizza Giuseppe Filomeni Elena Papaleo |
| author_facet | Emmanuelle Bignon Salvatore Rizza Giuseppe Filomeni Elena Papaleo |
| author_sort | Emmanuelle Bignon |
| collection | DOAJ |
| description | Nitric oxide (NO) is an essential signaling molecule in the regulation of multiple cellular processes. It is endogenously synthesized by NO synthase (NOS) as the product of L-arginine oxidation to L-citrulline, requiring NADPH, molecular oxygen, and a pterin cofactor. Two NOS isoforms are constitutively present in cells, nNOS and eNOS, and a third is inducible (iNOS). Despite their biological relevance, the details of their complex structural features and reactivity mechanisms are still unclear. In this review, we summarized the contribution of computational biochemistry to research on NOS molecular mechanisms. We described in detail its use in studying aspects of structure, dynamics and reactivity. We also focus on the numerous outstanding questions in the field that could benefit from more extensive computational investigations. Keywords: Nitric oxide synthase, computational methods, molecular mechanisms, redox regulation |
| first_indexed | 2024-12-10T11:34:12Z |
| format | Article |
| id | doaj.art-0328ef81bc3d475ea82391590e97aa43 |
| institution | Directory Open Access Journal |
| issn | 2001-0370 |
| language | English |
| last_indexed | 2024-12-10T11:34:12Z |
| publishDate | 2019-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Computational and Structural Biotechnology Journal |
| spelling | doaj.art-0328ef81bc3d475ea82391590e97aa432022-12-22T01:50:28ZengElsevierComputational and Structural Biotechnology Journal2001-03702019-01-0117415429Use of Computational Biochemistry for Elucidating Molecular Mechanisms of Nitric Oxide SynthaseEmmanuelle Bignon0Salvatore Rizza1Giuseppe Filomeni2Elena Papaleo3Computational Biology Laboratory, Danish Cancer Society Research Center, Strandboulevarden 49, 2100 Copenhagen, Denmark; Corresponding author.Redox Signaling and Oxidative Stress Group, Cell Stress and Survival Unit, Danish Cancer Society Research Center, Strandboulevarden 49, 2100 Copenhagen, DenmarkRedox Signaling and Oxidative Stress Group, Cell Stress and Survival Unit, Danish Cancer Society Research Center, Strandboulevarden 49, 2100 Copenhagen, Denmark; Department of Biology, University of Rome Tor Vergata, Rome, ItalyComputational Biology Laboratory, Danish Cancer Society Research Center, Strandboulevarden 49, 2100 Copenhagen, Denmark; Translational Disease Systems Biology, Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Protein Research University of Copenhagen, Copenhagen, Denmark; Corresponding author at: Computational Biology Laboratory, Danish Cancer Society Research Center, Strandboulevarden 49, 2100 Copenhagen, Denmark.Nitric oxide (NO) is an essential signaling molecule in the regulation of multiple cellular processes. It is endogenously synthesized by NO synthase (NOS) as the product of L-arginine oxidation to L-citrulline, requiring NADPH, molecular oxygen, and a pterin cofactor. Two NOS isoforms are constitutively present in cells, nNOS and eNOS, and a third is inducible (iNOS). Despite their biological relevance, the details of their complex structural features and reactivity mechanisms are still unclear. In this review, we summarized the contribution of computational biochemistry to research on NOS molecular mechanisms. We described in detail its use in studying aspects of structure, dynamics and reactivity. We also focus on the numerous outstanding questions in the field that could benefit from more extensive computational investigations. Keywords: Nitric oxide synthase, computational methods, molecular mechanisms, redox regulationhttp://www.sciencedirect.com/science/article/pii/S2001037018303465 |
| spellingShingle | Emmanuelle Bignon Salvatore Rizza Giuseppe Filomeni Elena Papaleo Use of Computational Biochemistry for Elucidating Molecular Mechanisms of Nitric Oxide Synthase Computational and Structural Biotechnology Journal |
| title | Use of Computational Biochemistry for Elucidating Molecular Mechanisms of Nitric Oxide Synthase |
| title_full | Use of Computational Biochemistry for Elucidating Molecular Mechanisms of Nitric Oxide Synthase |
| title_fullStr | Use of Computational Biochemistry for Elucidating Molecular Mechanisms of Nitric Oxide Synthase |
| title_full_unstemmed | Use of Computational Biochemistry for Elucidating Molecular Mechanisms of Nitric Oxide Synthase |
| title_short | Use of Computational Biochemistry for Elucidating Molecular Mechanisms of Nitric Oxide Synthase |
| title_sort | use of computational biochemistry for elucidating molecular mechanisms of nitric oxide synthase |
| url | http://www.sciencedirect.com/science/article/pii/S2001037018303465 |
| work_keys_str_mv | AT emmanuellebignon useofcomputationalbiochemistryforelucidatingmolecularmechanismsofnitricoxidesynthase AT salvatorerizza useofcomputationalbiochemistryforelucidatingmolecularmechanismsofnitricoxidesynthase AT giuseppefilomeni useofcomputationalbiochemistryforelucidatingmolecularmechanismsofnitricoxidesynthase AT elenapapaleo useofcomputationalbiochemistryforelucidatingmolecularmechanismsofnitricoxidesynthase |